PMID:15659391

Citation	Harris, MB, Mostecki, J and Rothman, PB (2005) Repression of an interleukin-4-responsive promoter requires cooperative BCL-6 function. J. Biol. Chem. 280:13114-21
Abstract	BCL-6 functions as a potent transcriptional repressor that binds with specificity to DNA elements bearing marked similarity to STAT recognition sequences. Previous studies have demonstrated that BCL-6 and Stat6 can both bind and regulate the Iepsilon promoter that controls immunoglobulin heavy chain class switching to IgE. Examination of BCL-6-/- and BCL-6-/-Stat6-/- mice has demonstrated that BCL-6 is a repressor of IgE and that Stat6 is still required for the interleukin-4 (IL-4) induction of class switching to IgE in B cells lacking BCL-6. To define the mechanisms by which BCL-6 represses IL-4 function, we analyzed the role of BCL-6 in repressing the Iepsilon promoter. There are three BCL-6-binding sites within this IL-4-responsive promoter. Analysis of Iepsilon promoters that have mutated BCL-6-binding sites demonstrates that at least two of these sites are required for maximal BCL-6 repression of this locus. Footprinting analysis demonstrates that BCL-6 binds cooperatively to the two upstream binding sites in the Iepsilon promoter. This cooperative binding requires the POZ domain of BCL-6. Furthermore, activated Stat6 molecules can displace BCL-6 from one of these binding sites. These data demonstrate that cooperative interaction between BCL-6 molecules is required for repression of the Iepsilon promoter.
Links	PubMed Online version:10.1074/jbc.M412649200
Keywords	Animals; Binding Sites; Binding, Competitive; CCAAT-Enhancer-Binding Protein-beta/metabolism; Cell Line; DNA-Binding Proteins/metabolism; DNA-Binding Proteins/physiology; Deoxyribonuclease I/metabolism; Genes, Reporter; Glutathione Transferase/metabolism; Interleukin-4/antagonists & inhibitors; Interleukin-4/genetics; Mice; Mutation; Plasmids/metabolism; Promoter Regions, Genetic; Protein Binding; Protein Structure, Tertiary; Proto-Oncogene Proteins/metabolism; Proto-Oncogene Proteins/physiology; Proto-Oncogene Proteins c-bcl-6; Recombinant Proteins/chemistry; Transcription Factors/metabolism; Transcription Factors/physiology; Transcription, Genetic; Transfection
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